Pollen–Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges
Abstract
:Featured Application
Abstract
1. Introduction
2. Food Allergens
3. PFAS Epidemiology
4. PFAS Pathogenesis
5. PFAS Symptoms and Effect on Quality of Life
6. Protein Families Involved in PFAS
6.1. Pathogenesis-Related Protein Group 10 (PR-10 Proteins)
6.2. Profilins
6.3. Lipid Transfer Proteins (LTPs)
6.4. Gibberellin-Regulated Proteins (GRPs)
6.5. Thaumatin-like Proteins (TLPs)
6.6. β-1,3-Glucanases
6.7. Isoflavonoid Reductases (IFRs)
7. PFAS Diagnosis
7.1. Skin Prick Testing (SPT)
7.2. Component-Resolved Diagnostics (CRD)
7.3. Basophil Activation Test (BAT)
7.4. Oral Food Challenge (OFC)
- Verify clinical reactions: it determines whether symptoms like oral itching, tingling, or swelling occur after consuming a suspected food [211].
- Differentiate between allergies: OFC distinguishes PFAS, typically caused by labile proteins like PR-10 or profilins, from primary food allergies associated with stable proteins like storage proteins [212].
- Guide dietary management: by identifying tolerable foods, OFC helps avoid unnecessary dietary restrictions, improving patients’ quality of life [98].
7.5. Exploratory Approaches in Food Allergy Testing
7.5.1. Mast Cell Activation Test (MAT)
7.5.2. Allergen-Specific IgG4 and IgA
7.5.3. Bead-Based Epitope Assays (BBEA)
7.5.4. Glycosylation Analysis
7.5.5. Microbiome Analysis
7.5.6. Artificial Intelligence (AI)
8. PFAS Management
8.1. Food Avoidance
8.2. Pharmacological Treatment
8.3. Allergen Immunotherapy (AIT)
- Shift in immune response: during an allergic reaction, the immune system predominantly produces IgE antibodies, which bind to mast cells and basophils, triggering the release of histamine and other inflammatory mediators. AIT induces a class-switch in antibody production from allergen-specific IgE to IgG4, a blocking antibody that prevents allergen-IgE binding, shifting the balance from a Th2-dominant response, characterized by IgE production, to a Th1-dominant response and Treg activation. This reduces the activation of mast cells and basophils. The production of blocking antibodies, such as IgG4, plays a key role in neutralizing allergens before they can trigger IgE-mediated reactions [261,262].
- T-cell modulation: AIT promotes the development of regulatory T cells (Tregs), which suppress allergic inflammation by releasing anti-inflammatory cytokines such as IL-10 and TGF-β. These cytokines reduce the activity of effector T-helper 2 (Th2) cells, which are responsible for producing IgE and driving allergic inflammation [260].
- Dendritic cell modulation: dendritic cells exposed to allergens in the presence of AIT shift their cytokine production profile to favor tolerance rather than sensitization. This further supports the suppression of Th2 responses and enhances the induction of Tregs [262].
- Long-term tolerance: over time, AIT leads to the reprogramming of the immune system, resulting in long-lasting tolerance to allergens even after discontinuation of treatment. This effect distinguishes AIT from symptomatic treatments like antihistamines [263].
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Allergen Source | Plant Family | Pathogenesis-Related 10 (PR-10) | Profilin | Lipid Transfer Protein (LTP) | Gibberellin-Regulated Protein (GRP) | Thaumatin-like Protein (TLP) | β-1,3-Glucanase | Isoflavonoid Reductase |
---|---|---|---|---|---|---|---|---|
Birch pollen (Betula pendula Roth) | Betulaceae | Bet v 1 | Bet v 2 | - | - | - | - | Bet v 6 |
Hazel pollen (Corylus avellana L.) | Betulaceae | Cor a 1 | Cor a 2 | Cor a 8 | - | - | - | Cor a 6 |
Grass pollen (Phleum pratense L.) | Poaceae | - | Phl p 12 | - | - | - | - | - |
Olive pollen (Olea europaea L.) | Oleaceae | - | Ole e 2 | Ole e 7 | - | Ole e 13 | Ole e 9 | Ole e 12 |
Japanese cedar pollen (Cryptomeria japonica (Thunb. ex L.f.) D.Don) | Cupressaceae | - | - | - | Cry j 7 | Cry j 3 | - | - |
Mediterranean cypress pollen (Cupressus sempervirens L.) | Cupressaceae | - | - | - | Cup s 7 | Cup s 3 | - | - |
Common ragweed pollen (Ambrosia artemisiifolia L.) | Asteraceae | - | Amb a 8 | Amb a 6 | - | - | - | - |
Mugwort pollen (Artemisia vulgaris L.) | Asteraceae | Art v 2 | Art v 4 | Art v 3 | - | - | - | - |
Pellitory-of-the-wall (Parietaria Judaica L.) | Urticaceae | - | Par j 3 | Par j 1, Par j 2 | - | - | - | - |
Apple (Malus domestica (Suckow) Borkh.) | Rosaceae | Mal d 1 | Mal d 4 | Mal d 3 | - | Mal d 2 | - | - |
Peach (Prunus persica (L.) Batsch) | Rosaceae | Pru p 1 | Pru p 4 | Pru p 3 | Pru p 7 | Pru p 2 | - | - |
Cherry (Prunus avium L.) | Rosaceae | Pru av 1 | Pru av 4 | Pru av 3 | Pru av 7 | Pru av 2 | - | - |
Plum (Prunus domestica L.) | Rosaceae | Pru d 1 | Pru d 4 | Pru d 3 | - | Pru d 2 | - | - |
Almond (Prunus dulcis Batsch) | Rosaceae | - | - | Pru du 3 | - | - | - | - |
Pear (Pyrus communis L.) | Rosaceae | Pyr c 1 | Pyr c 4 | Pyr c 3 | - | - | - | Pyr c 5 |
Strawberry (Fragaria × ananass Duchesne) | Rosaceae | Fra a 1 | Fra a 4 | Fra a 3 | - | - | Fra a Glucanase | - |
Orange (Citrus × sinensis (L.) Osbeck) | Rutaceae | - | Cit s 2 | Cit s 3 | Cit s 7 | - | - | Cit s IFR |
Grape (Vitis vinifera L.) | Vitaceae | - | Vit v 4 | Vit v 1 | - | Vit v TLP | Vit v Glucanase | - |
Tomato (Solanum lycopersicum L.) | Solanaceae | Sola l 4 | Sola l 1 | Sola l 3, Sola l 6, Sola l 7 | - | Sola l TLP | Sola l Glucanase | - |
Bell pepper (Capsicum annuum L.) | Solanaceae | - | Cap a 2 | - | Cap a 7 | Cap a 1 | Cap a Glucanase | - |
Banana (Musa acuminata Colla) | Musaceae | - | Mus a 1 | Mus a 3 | - | Mus a 4 | Mus a 5 | - |
Celery (Apium graveolens L.) | Apiaceae | Api g 1 | Api g 4 | Api g 2 | - | - | - | - |
Carrot (Daucus carota subsp. Sativus (Hoffm.) Schübl. and G. Martens) | Apiaceae | Dau c 1 | Dau c 4 | - | - | - | - | Dau c 5 |
Walnut (Juglans regia L.) | Juglandaceae | Jug r 5 | Jug r 7 | Jug r 3, Jug r 8 | - | Jug r TLP | - | - |
Kiwi (Actinidia deliciosa (A.Chev.) C.F.Liang and A.R.Ferguson) | Actinidiaceae | Act d 8, Act d 11 | Act d 9 | Act d 10 | - | Act d 2 | - | - |
Sunflower (Helianthus annuus L.) | Asteraceae | - | Hel a 2 | Hel a 3 | - | - | - | - |
Soybean (Glycine max (L.) Merr.) | Fabaceae | Gly m 4 | Gly m 3 | - | - | - | - | - |
Peanut (Arachis hypogaea L.) | Fabaceae | Ara h 8 | Ara h 5 | Ara h 9, Ara h 16, Ara h 17 | - | - | - | - |
Barley (Hordeum vulgare L.) | Poaceae | - | Hor v 12 | Hor v 14, Hor v 7k-LTP | - | - | - | - |
Wheat (Triticum aestivum L.) | Poaceae | - | Tri a 12 | Tri a 14 | - | - | - | - |
Rice (Oryza sativa L.) | Poaceae | - | Ory s 12 | - | - | - | - | - |
Corn (Zea mays L.) | Poaceae | - | Zea m 12 | Zea m 14 | - | Zea m TLP | - | - |
Category | Description | Details/Insights |
---|---|---|
Strengths | ||
Rapid results | SPT provides immediate feedback, allowing clinicians to correlate findings with the patient’s clinical history during the same visit. | Results are available within 15–20 min, making it an efficient diagnostic tool. |
Minimally invasive | The test is simple, safe, and well-tolerated by most patients. | Requires only a small lancet and allergen extract, with minimal discomfort for the patient. |
Broad applicability | SPT can assess sensitization to a wide range of pollens and foods in a single session, making it a comprehensive diagnostic tool for PFAS. | Ideal for identifying multiple allergens simultaneously, including pollens and related foods. |
High sensitivity | When combined with fresh food testing, SPT achieves high sensitivity for detecting relevant allergens in PFAS. | Fresh food testing helps identify heat-labile proteins like PR-10 proteins and profilins not always detected by extracts. |
Cost-effective | SPT is a relatively low-cost diagnostic tool compared to molecular diagnostics or in vitro IgE testing. | Widely available in clinical settings. |
Non-invasive follow-up | Enables ongoing monitoring of sensitization patterns without invasive procedures. | Can track allergen changes in response to therapy or environmental shifts. |
Limitations | ||
False negatives | Heat-labile proteins in PFAS, such as PR-10 proteins and profilins, may degrade in commercial extracts, leading to false negatives. | Fresh food testing is essential to overcome this limitation. |
Non-specific reactivity | Non-specific skin reactions or dermographism can complicate interpretation, necessitating careful control comparisons. | Negative and positive controls are critical for accurate interpretation. |
Requires expertise | Accurate interpretation of SPT results demands expertise to distinguish between primary sensitizations and cross-reactive allergies. | Specialized training is needed to correlate results with clinical history and dietary triggers. |
Limited specificity | Positive SPT results indicate sensitization but do not always confirm clinical allergy, as some sensitized individuals may remain asymptomatic. | Additional diagnostics, such as oral food challenges, may be needed to confirm clinical relevance. |
Risk of systemic reactions | Rarely, SPT may trigger systemic allergic reactions, especially in highly sensitized individuals. | Emergency medications (e.g., epinephrine) should be readily available during testing. |
Geographic variability | Allergen extracts may not represent local or regional allergen sources accurately, leading to incomplete diagnostic coverage. | Custom extracts may be needed for certain endemic allergens. |
Heading | ImmunoCAP | ISAC (Immuno Solid-Phase Allergen Chip; ThermoFisher Scientific, Waltham, MA, USA) | ALEX (Allergy Xplorer) |
---|---|---|---|
How It Works | Singleplex assay that measures IgE to one allergen or component per test. | Multiplex assay testing IgE to > 100 allergenic components on a microarray chip. | Multiplex assay testing IgE to > 300 whole allergens and molecular components on an allergen array. |
Uses a solid-phase system with allergens immobilized on a cellulose sponge matrix. | Uses purified allergens immobilized on a chip, requiring minimal serum (20–30 μL). | Integrates whole extracts and components with cross-reactivity inhibition for higher specificity. | |
Results are quantitative (kU/L). | Results are semi-quantitative (fluorescence intensity levels). | Results are semi-quantitative and integrate cross-reactivity adjustments. | |
Advantages | |||
Quantitative results | Provides precise measurements of IgE levels, helping assess sensitization and risk. | Semi-quantitative results allow broad allergen screening and cross-reactivity insights. | Semi-quantitative results combined with inhibition testing improve specificity for genuine sensitization. |
Comprehensive testing | Wide library of allergens, including region-specific ones. | Simultaneous testing for > 100 allergenic components across pollens, foods, and other sources. | Tests > 300 allergens, covering both whole extracts and components for comprehensive profiling. |
Sensitivity and specificity | High sensitivity and specificity for targeted allergens. | Ideal for identifying cross-reactivity due to panallergens like PR-10, profilins, and LTPs. | High specificity through cross-reactivity inhibition technology. |
Ease of use | Widely available, standardized, and reproducible across labs. | Requires minimal serum and provides a complete sensitization overview. | User-friendly data presentation with clear insights into primary and cross-reactive sensitizations. |
Limitations | |||
Cost | Can be expensive for multiple allergens or components. | Expensive but cost-effective for complex allergy cases. | Relatively expensive but efficient for patients with complex or multiple suspected allergies. |
Result format | Quantitative results are easy to interpret. | Semi-quantitative results require experienced interpretation to correlate with clinical relevance. | Semi-quantitative results may lack the precision needed for exact risk assessment. |
Component limitations | Limited to clinician-selected allergens or components; rare ones may be unavailable. | Does not include all region-specific allergens, limiting coverage in some cases. | Some rare or region-specific allergens may be absent. |
Serum requirement | Requires a larger volume of serum for testing multiple allergens. | Requires minimal serum (20–30 μL). | Requires a low volume of serum (100 μL). |
Applications in PFAS | |||
Identifying panallergens | Effective for targeted testing of panallergens like PR-10 proteins, profilins, and LTPs. | Simultaneously identifies sensitization to multiple panallergens like PR-10 proteins, profilins, and LTPs. | Covers a wide range of panallergens, integrating whole extracts and components for detailed insights. |
Primary vs. cross-reactivity | Differentiates primary food allergies from cross-reactivity with pollens. | Broad allergen panel helps identify patterns of cross-reactivity across multiple allergen sources. | Combines whole extracts and components to distinguish primary sensitization from cross-reactivity. |
Risk stratification | Quantitative results enable detailed risk assessment (e.g., Ara h 2 for severe peanut allergy). | Helps determine risk based on allergen stability (e.g., PR-10 for mild symptoms, LTPs for systemic reactions). | Identifies risk by combining sensitization profiles with cross-reactivity inhibition for stability insights. |
Guiding dietary advice | Ideal for providing specific advice based on IgE levels to individual allergens. | Identifies panallergen sensitization, enabling tailored dietary recommendations (e.g., raw vs. cooked tolerance). | Integrates sensitization profiles to guide personalized dietary and exposure advice. |
Supporting immunotherapy | Identifies primary allergens for allergen immunotherapy (e.g., Bet v 1 for birch). | Helps guide allergen immunotherapy decisions by clarifying primary sensitization patterns. | Assists in AIT decisions by revealing sensitization to multiple relevant allergens. |
Insights/Observations | |||
Special use cases | Ideal for monitoring sensitization over time or tracking therapy response. | Best for initial screening of complex cases or polysensitization. | Excellent for broad sensitization profiling in patients with multiple or unclear triggers. |
Comparative edge | Best for precise, targeted testing and long-term tracking of IgE levels. | Ideal for comprehensive overviews in patients with complex allergic profiles. | Combines extract- and component-based testing with cross-reactivity inhibition for higher specificity. |
Category | Details | Additional Insights |
---|---|---|
Advantages of OFC | ||
High diagnostic accuracy | OFC directly confirms the clinical relevance of sensitization detected through other diagnostic tests, making it the gold standard for PFAS. | Particularly valuable when SPT or specific IgE results are inconclusive. |
Personalized management | Results guide tailored dietary recommendations, allowing patients to safely consume tolerable foods while avoiding problematic ones. | Reduces patient anxiety by clarifying which foods are safe in raw or cooked forms. |
Minimizing dietary restrictions | OFC helps prevent unnecessary avoidance of foods, improving nutrition and quality of life. | Expands dietary options and supports balanced nutrition, especially in children and individuals with multiple food restrictions. |
Clarity in complex cases | In polysensitized patients, OFC identifies specific triggers among cross-reactive allergens. | Essential for differentiating between cross-reactivity and primary food allergies. |
Limitations of OFC | ||
Resource-intensive | OFC requires trained personnel, controlled environments, and significant time, making it less accessible in routine practice. | Requires specialized facilities, which may not be available in all healthcare settings. |
Risk of reactions | Although PFAS reactions are typically mild, the risk of unexpected systemic reactions necessitates close medical supervision. | Emergency treatments such as epinephrine must be readily available. |
Subjectivity | Open challenges may introduce bias, particularly for subjective symptoms like itching or tingling. | Blinded challenges (e.g., single- or double-blind) can help reduce bias. |
Patient anxiety | The prospect of consuming a suspected allergen can cause anxiety, which may complicate interpretation of symptoms. | Proper counseling and reassurance can help mitigate patient concerns before the challenge. |
Drug Name | Generation | Formulation | Onset of Action | Duration of Action | Sedation Potential | Common Uses in Allergies |
---|---|---|---|---|---|---|
Diphenhydramine | First | Oral, Injectable | 15–30 min | 4–6 h | High | Acute allergic reactions, anaphylaxis adjunct |
Chlorpheniramine | First | Oral | 30 min | 4–6 h | Moderate | Allergic rhinitis, mild allergic reactions |
Hydroxyzine | First | Oral, Injectable | 15–30 min | 4–6 h | High | Anxiety-related itching, urticaria |
Cetirizine | Second | Oral | 1 h | 24 h | Low | PFAS, allergic rhinitis, urticaria |
Levocetirizine | Second | Oral | 1 h | 24 h | Very Low | PFAS, chronic urticaria, allergic rhinitis |
Loratadine | Second | Oral | 1–3 h | 24 h | Minimal | PFAS, allergic rhinitis |
Desloratadine | Second | Oral | 1–3 h | 24 h | Minimal | PFAS, chronic idiopathic urticaria |
Fexofenadine | Second | Oral | 1 h | 24 h | None | PFAS, seasonal allergic rhinitis |
Rupatadine | Second | Oral | 1–2 h | 24 h | Very Low | PFAS, chronic urticaria, allergic rhinitis |
Bilastine | Second | Oral | 1 h | 24 h | None | PFAS, allergic rhinoconjunctivitis |
Ebastine | Second | Oral | 1–3 h | 24 h | Low | Chronic urticaria, allergic rhinitis |
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Haidar, L.; Bănărescu, C.F.; Uța, C.; Moldovan, S.I.; Zimbru, E.-L.; Zimbru, R.-I.; Ciurariu, E.; Georgescu, M.; Panaitescu, C. Pollen–Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges. Appl. Sci. 2025, 15, 66. https://doi.org/10.3390/app15010066
Haidar L, Bănărescu CF, Uța C, Moldovan SI, Zimbru E-L, Zimbru R-I, Ciurariu E, Georgescu M, Panaitescu C. Pollen–Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges. Applied Sciences. 2025; 15(1):66. https://doi.org/10.3390/app15010066
Chicago/Turabian StyleHaidar, Laura, Camelia Felicia Bănărescu, Cristina Uța, Sandra Iulia Moldovan, Elena-Larisa Zimbru, Răzvan-Ionuț Zimbru, Elena Ciurariu, Marius Georgescu, and Carmen Panaitescu. 2025. "Pollen–Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges" Applied Sciences 15, no. 1: 66. https://doi.org/10.3390/app15010066
APA StyleHaidar, L., Bănărescu, C. F., Uța, C., Moldovan, S. I., Zimbru, E. -L., Zimbru, R. -I., Ciurariu, E., Georgescu, M., & Panaitescu, C. (2025). Pollen–Food Allergy Syndrome: Allergens, Clinical Insights, Diagnostic and Therapeutic Challenges. Applied Sciences, 15(1), 66. https://doi.org/10.3390/app15010066